title: A role for V-ATPase subunits in synaptic vesicle fusion?
abstract: SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptors)-mediated exocytotic release of neurotransmitters is a key process in neuronal communication, controlled by a number of molecular interactions. A synaptic vesicle v-SNARE protein (VAMP2 or synaptobrevin), in association with two plasma membrane t-SNAREs (syntaxin 1 and SNAP25), assemble to form a protein complex that is largely accepted as the minimal membrane fusion machine. Acidification of the synaptic vesicle lumen by the large multi-subunit vacuolar proton pump (V-ATPase) is required for loading with neurotransmitters. Recent data demonstrate a direct interaction between the c-subunit of the V-ATPase and VAMP2 that appears to play a role at a late step in transmitter release. In this review, we examine evidence suggesting that the V0 membrane sector of the V-ATPase not only participates in proton pumping, but plays a second distinct role in neurosecretion, downstream of filling and close to vesicle fusion.
authors.affiliation: INSERM U641, Marseille, France. oussama.elfar@univmed.fr
authors.forename: Oussama
authors.initials: O
authors.lastname: El Far
authors.forename: Michael
authors.initials: M
authors.lastname: Seagar
mesh_terms: D000818:Animals; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D017494:Proton Pumps / Q000235:genetics / Q000378:metabolism; D050600:SNARE Proteins / Q000378:metabolism; D013570:Synaptic Membranes / Q000201:enzymology / Q000378:metabolism; D013572:Synaptic Vesicles / Q000201:enzymology* / Q000502:physiology* / Q000648:ultrastructure; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D050827:Syntaxin 1 / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D017494:Proton Pumps; D050600:SNARE Proteins; D050825:Synaptosomal-Associated Protein 25; D050827:Syntaxin 1; D050988:Vesicle-Associated Membrane Protein 2; D025262:Vacuolar Proton-Translocating ATPases